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CME / ABIM MOC / CE

Does Orthostatic Hypertension in Young Adults Predict Major Cardiac Events?

  • Authors: News Author: Patrice Wendling; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 5/6/2022
  • Valid for credit through: 5/6/2023
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0 contact hours are in the area of pharmacology)

    Pharmacists - 0.25 Knowledge-based ACPE (0.025 CEUs)

    Physician Assistant - 0.25 AAPA hour(s) of Category I credit

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

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    • Letter of Completion
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Target Audience and Goal Statement

This activity is intended for cardiologists, internists, family medicine and primary care clinicians, nurses, pharmacists, public health and prevention officials, physician assistants, and other members of the healthcare team for younger adults with hypertension who may be at risk for major cardiac adverse events (MACE).

The goal of this activity is that learners will be better able to describe the association of orthostatic hyperreactivity with major adverse cardiovascular (MACE) and renal events in a cohort of young hypertensive patients enrolled in the prospective multicenter HARVEST study that began in Italy in 1990.

Upon completion of this activity, participants will:

  • Describe the association of orthostatic hyperreactivity with MACE, according to a prospective cohort study of young hypertensive patients
  • Determine clinical and public health implications of the association of orthostatic hyperreactivity with MACE, according to a prospective cohort study of young hypertensive patients
  • Outline implications for the healthcare team


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News Author

  • Patrice Wendling

    Deputy News Editor
    Medscape Medical News

    Disclosures

    Disclosure: Patrice Wendling has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed the following relevant financial relationships:
    Stocks, stock options, or bonds: AbbVie Inc. (former)

Editor/Nurse Planner

  • Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Leigh A. Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Amanda Jett, PharmD, BCACP, has disclosed no relevant financial relationships.

PA Planner

  • Jennifer Hakkarainen, PA-C

    Medical Education Director, Medscape, LLC

    Disclosures

    Disclosure: Jennifer Hakkarainen, PA-C, has disclosed no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.


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CME / ABIM MOC / CE

Does Orthostatic Hypertension in Young Adults Predict Major Cardiac Events?

Authors: News Author: Patrice Wendling; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 5/6/2022

Valid for credit through: 5/6/2023

processing....

Clinical Context

Among elderly adults with hypertension, orthostatic hypotension when standing is prevalent and predicts future cardiovascular (CV) events and mortality. Orthostatic changes in blood pressure (BP) and their significance among younger adults have historically been poorly characterized. In a recently published study of over 1200 young to middle age participants with untreated stage 1 hypertension, the current method of BP measurement taken while the patient is sitting may need to be reconsidered. If major adverse cardiovascular events (MACE) have the potential of being predicted with a routine office visit, members of the healthcare team, especially in primary care settings, may be more capable of providing an early diagnosis and intervention to improve future patient outcomes.

Study Synopsis and Perspective

A sudden drop in BP when standing is a common and concerning problem in elderly hypertensive people. Now, research suggests a large BP swing in the opposite direction on standing may be equally concerning in younger hypertensive people.

Young and middle-aged adults with a systolic blood pressure (SBP) response to standing > 6.5 mm Hg had almost double the risk for MACE during follow-up compared with other participants.

An exaggerated BP response remained an independent predictor of MACE, even after adjusting for traditional risk factors, including 24-hour BP, the study showed.

"The clinical implication is important because now doctors measure [BP] in young people in the upright posture, but what we say is it must be measured also while standing," said Paolo Palatini, MD, a professor of internal medicine at the University of Padova, Padova, Italy, who led the study.

Previous studies have found that an exaggerated BP response to standing is a predictor of future hypertension, CV events, and mortality particularly in older patients, but few prognostic data exist in persons who are young to middle age, he noted.

The study, published March 17 in Hypertension, included 1207 participants ages 18 to 45 years with untreated stage 1 hypertension (SBP 140-159 mm Hg or diastolic blood pressure 90-99 mm Hg) in the prospective multicenter HARVEST study that began in Italy in 1990. The mean age at enrollment was 33 ± 9 years.

Blood pressure was measured at 2 visits 2 weeks apart, with each visit including 3 supine measurements taken after the patient had laid down for a minimum of 5 minutes, followed by 3 standing measurements taken 1 minute apart.

According to the average of standing-lying BP differences during the 2 visits, participants were then classified as having a normal or exaggerated (top decile, lower limit > 6.5 mm Hg) SBP response to standing.

The 120 participants classified as "hyperreactors" averaged an 11.4-mm Hg SBP increase upon standing whereas the rest of the participants averaged a 3.8-mm Hg fall in SBP upon standing.

At their initial visit, hyperreactors were more likely to be smokers (32.1% vs 19.9%) and coffee drinkers (81.7% vs 73%) and to have ambulatory hypertension (90.8% vs 76.4%).

They were, however, no more likely to have a family history of CV events and had a lower supine SBP (140.5 mm Hg vs 146 mm Hg), lower total cholesterol (190.35 vs 196.07 mg/dL), and higher HDL-C.

Age, sex, and body mass index were similar between the two groups, as was BP variability, nocturnal BP dip, and the frequency of extreme dippers. Participants with a normal SBP response were more likely to be treated for hypertension during follow-up (81.7% vs 69.7%; P = .003).

In 630 participants who had catecholamines measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in hyperreactors than normal responders (118.4 ± 185.6 nmol/mol vs 77 ± 90.1 nmol/mol; P = .005t).

During a median follow-up of 17.3 years, there were 105 major CV events, broadly defined to include acute coronary syndrome (48), any stroke (13), heart failure requiring hospitalization (3), aortic aneurysms (3), peripheral vascular disease (6), chronic kidney disease (12), and permanent atrial fibrillation (AF) (20).

The near doubling of MACE risk among hyperreactors remained when AF was excluded and when 24-hour ambulatory SBP was included in the model, the author reported.

The results are in line with previous studies indicating that hyperreactors to standing have normal sympathetic activity at rest but an increased sympathetic response to stressors, observed Palatini and colleagues. This neurohumoral overshoot seems to be peculiar to young adults whereas vascular stiffness seems to be the driving mechanism of orthostatic hypertension in older adults.

If a young person's BP spikes upon standing, "then you have to treat them according to the average of the lying and the standing pressure," Palatini said. "In these people, [BP] should be treated earlier than in the past."

"The study is important because it identified a new marker for hypertension that is easily evaluated in clinical practice," Nieca Goldberg, MD, medical director of the Atria Institute and an associate professor of medicine at New York University Grossman School of Medicine, both in New York, New York, commented to Medscape via email.

She noted that standing BPs are usually not taken as part of a medical visit and, in fact, seated BPs are often taken incorrectly while the patient is seated on the exam table rather than with their feet on the floor and using the proper cuff size.

"By incorporating standing BP, we will improve our diagnosis for hypertension and with interventions, such as diet and exercise, salt reduction, and medication when indicated, lower risk for heart attack, stroke, heart failure, [and] kidney and eye disease," said Goldberg, who is also a spokesperson for the American Heart Association.

"The biggest barrier is that office visits are limited to 15 minutes and not enough time is spent on the vital signs," she noted. "We need changes to the healthcare system that value our ability to diagnose BP and take the time to counsel patients and explain treatment options."

Limitations of the present study are that 72.7% of participants were men and all were White, Palatini said. Future work is also needed to create a uniform definition of BP hyperreactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

The study was funded by the Association 18 Maggio 1370 in Italy. The authors have disclosed no relevant financial relationships. Goldberg reported being a spokesperson for the American Heart Association.

Hypertension. 2022;79:984-992.[1]

Study Highlights

  • Participants in this cohort study were 1207 untreated adults, aged 18 to 45 (mean, 33.1 ± 8.6) years who screened positive for stage I hypertension.
  • Orthostatic BP change was calculated as the difference between 6 standing and 6 supine BP readings obtained during 2 separate visits 2 weeks apart.
  • In the entire cohort, mean standing-supine SBP difference was −2.7 ± 7.3/4.6 ± 5.4 mm Hg.
  • Hyperreactivity to standing was defined as being in the top decile of standing-supine SBP difference (> 6.5 mm Hg).
  • Upon standing, SBP increased 11.4 ± 4.6 mm Hg on average among the 120 hyperreactors but decreased 3.8 ± 5.9 mm Hg on average among normoreactors.
  • At baseline, hyperreactors were more likely than normoreactors to be smokers (32.1% vs 19.9%) and coffee drinkers (81.7% vs 73%) and to have ambulatory hypertension on 24-hour recordings (90.8% vs 76.4%; P = .001) but not to have a family history of CV events.
  • Compared with normoreactors, hyperreactors had lower supine SBP (140.5 vs 146 mm Hg), lower total cholesterol (190.35 vs 196.07 mg/dL) and higher HDL-C (54.83 vs 52.12 mg/dL).
  • Age, sex, BMI, BP variability, nocturnal BP dip, and frequency of extreme dippers were similar in both groups.
  • Normoreactors were more likely to be treated for hypertension during follow-up (81.7% vs 69.7%; P = .003).
  • Among 630 participants who underwent 24-hour urinary catecholamine measurement, the epinephrine/creatinine ratio was higher in hyperreactors (118.4 ± 185.6 vs 77 ± 90.1 nmol/mol; P = .005t).
  • During 17.3-year follow-up, there were 105 MACE.
  • A multivariate Cox model showed that hyperreactivity to standing independently predicted MACE (HR 1.97 [95% CI: 1.1, 3.52]), even when excluding AF and adjusting for traditional risk factors, 24-hour ambulatory BP data and incident hypertension during follow-up.
  • The investigators concluded that in young to middle-aged hypertensive adults, exaggerated SBP response to standing is associated with sympatho-adrenergic hyperreactivity and independently predicts MACE during follow-up, with almost double the risk vs normoreactors.
  • The findings are similar to those of previous studies in which hyperreactors to standing had normal sympathetic activity at rest but increased sympathetic response to stressors.
  • Mostly young adults experience this neurohumoral overshoot whereas older adults mostly experience orthostatic hypotension driven by vascular stiffness.
  • Orthostatic BP testing is easily performed in clinical settings and offers prognostic information beyond ambulatory BP monitoring.
  • To detect hypertension earlier, clinicians should measure BP in young adults while standing and sitting.
  • Hyperreactors should be treated based on the average of their supine and standing pressure.
  • Incorporating standing BP into clinical assessment should improve diagnosis of hypertension and facilitate earlier lifestyle interventions and pharmacotherapy when indicated to reduce risk for myocardial infarction, stroke, heart failure, and renal and eye disease.
  • Study limitations include potential lack of generalizability to women and non-White racial/ethnic groups, as 72.7% of participants were men and all were White.
  • Future research should develop a uniform definition of BP hyperreactivity to standing, possibly based on risk estimates, for inclusion in future hypertension guidelines.

Clinical Implications

  • Exaggerated SBP response to standing in young hypertensive adults independently predicts MACE during follow-up.
  • Orthostatic BP testing is easily performed in clinical settings and offers prognostic information beyond ambulatory BP monitoring.
  • Implications for the Healthcare Team: Hyperreactors should be treated based on the average of their supine and standing pressure.

 

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